A novel synthetic approach to the synthesis of enantiomerically pure 2,5-disubstituted pyrrolines is described. The methodology involves a Ag-catalyzed 5-endo-dig cyclization of enantiopure aryl-substituted acetylene-containing amino acids. It has also been shown that the obtained pyrrolines can be efficiently transformed into the corresponding saturated 5-aryl-substituted proline derivatives.

This article provides an overview of the literature concerning synthetic applications of unsaturated aliphatic amino acids in the period May 2000 to December 2004.

[reaction: see text] Both unsaturated proline derivatives and optically active tryptophan analogues have been obtained via Pd-catalyzed cyclization of aniline-containing acetylenic amino acids. The side chain length of the cyclization precursor determines which one of the two possible products will be formed.

A synthetic approach to the synthesis of novel tryptophan derivatives and benzofuran-containing amino acids is detailed. The sequence starts from enzymatically resolved enantiopure acetylene-containing amino acids, of which the acetylene function can be efficiently transformed into the targeted 2-substited indole and benzofuran moieties via Sonogashira-type coupling and metal-catalyzed cyclization.

A series of cyclic enediyne-containing amino acids with ring sizes varying from 10 to 12 atoms have been prepared starting from propargylglycine and homopropargylglycine. Their reactivity towards Bergman cyclisation under elevated temperatures has been explored. The enediynes displayed marked differences in cyclisation half-lives depending on the olefinic substituent and the ring size. A potential candidate for incorporation into peptides has been identified.